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Posted On: 03/19/2024 9:10:55 PM
Post# of 148870
Looking into Glioblastoma and Albert Einstein’s just cuz I’m bored. Found an interesting through line. Give me a second to explain. The axis is Cancer Associated Fibroblasts, CAFs. First in Glioblastoma (GB) at Albert Einstein, and second in Heptatocellar Carcinoma (HCC), particularly CCL5 excretion by CAFs in HCC. It may partially explain a reason for the Lalezari’s partnership in testing LL in mice, in Glioblastoma, at Albert Einstein.
Here’s a link to GB at Albert Einsteins.
https://www.einsteinmed.edu/research-briefs/1...ma-tumors/
Here’s a link to the HCC article.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119971/
Interesting connections to me at least, first Albert Einstein and second HCC.
“ Using high-throughput single-cell RNA sequencing data analysis and other techniques, Deyou Zheng, Ph.D., Xingxing Zang, Ph.D., and colleagues identified CAFs in human glioblastoma tumors and found that increased CAF abundance in glioblastoma correlates with higher tumor grades and worse clinical outcomes. The work, led by Phillip M. Galbo Jr., a recently graduated Einstein Ph.D. student, also showed that fibronectin—a protein secreted by CAFs—promotes the migration and invasion of glioblastoma cells. The study shows that CAFs, although present in small numbers in glioblastomas, appear to play important roles in tumor development and aggressiveness, and may make tumors resistant to chemotherapy. The findings indicate that strategies targeting CAFs may improve the treatment of glioblastomas. The study was published online on December 7 in Clinical Cancer Research.”
And from HCC, “ Cancer associated fibroblast–derived CCL5 promotes hepatocellular carcinoma metastasis through activating HIF1α/ZEB1 axis”
“ Cancer-associated fibroblasts (CAFs) are one of the most enriched components of Hepatocellular carcinoma (HCC) microenvironment, which are tightly related to the metastasis and invasion of HCC. We identified a mechanism by which CAF-derived chemokine CCL5 enhanced HCC metastasis by triggering the HIF1α/ZEB1 axis. We demonstrated that CAFs derived from HCC tissues promoted the migration and invasion of HCC cells and facilitated metastasis to the lung of NOD/SCID mice. Then the chemokine antibody array elucidated the higher chemokine CCL5 level secreted by CAFs than by paracancerous tissue fibroblasts (PTFs). Mechanistically, we found that CAF-derived CCL5 inhibited the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF1α) by binding to specific receptors, maintained HIF1α under normoxia, thereby up-regulated the downstream gene zinc finger enhancer-binding protein 1 (ZEB1) and induced epithelial-mesenchymal transition (EMT), ultimately validating its ability to promote lung metastasis of HCC. And this novel mechanism may have association with poor prognosis. Taken together, targeting CAF-derived CCL5 mediated HIF1α/ZEB1 cascade possibly propose a new therapeutic route for HCC.”
I certainly don’t know about the HIF1α/ZEB1 axis, but maybe worth a discussion since there’s not much else to talk about. Certainly the data coming from a mouse study will be preliminary and not move any needles soon. But looks like CCR5 blockade of CAF secreted CCL5 may play a role in angiogenesis and poor poor/better prognosis in Glioblastoma at Albert Einstein's.
Here’s a link to GB at Albert Einsteins.
https://www.einsteinmed.edu/research-briefs/1...ma-tumors/
Here’s a link to the HCC article.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119971/
Interesting connections to me at least, first Albert Einstein and second HCC.
“ Using high-throughput single-cell RNA sequencing data analysis and other techniques, Deyou Zheng, Ph.D., Xingxing Zang, Ph.D., and colleagues identified CAFs in human glioblastoma tumors and found that increased CAF abundance in glioblastoma correlates with higher tumor grades and worse clinical outcomes. The work, led by Phillip M. Galbo Jr., a recently graduated Einstein Ph.D. student, also showed that fibronectin—a protein secreted by CAFs—promotes the migration and invasion of glioblastoma cells. The study shows that CAFs, although present in small numbers in glioblastomas, appear to play important roles in tumor development and aggressiveness, and may make tumors resistant to chemotherapy. The findings indicate that strategies targeting CAFs may improve the treatment of glioblastomas. The study was published online on December 7 in Clinical Cancer Research.”
And from HCC, “ Cancer associated fibroblast–derived CCL5 promotes hepatocellular carcinoma metastasis through activating HIF1α/ZEB1 axis”
“ Cancer-associated fibroblasts (CAFs) are one of the most enriched components of Hepatocellular carcinoma (HCC) microenvironment, which are tightly related to the metastasis and invasion of HCC. We identified a mechanism by which CAF-derived chemokine CCL5 enhanced HCC metastasis by triggering the HIF1α/ZEB1 axis. We demonstrated that CAFs derived from HCC tissues promoted the migration and invasion of HCC cells and facilitated metastasis to the lung of NOD/SCID mice. Then the chemokine antibody array elucidated the higher chemokine CCL5 level secreted by CAFs than by paracancerous tissue fibroblasts (PTFs). Mechanistically, we found that CAF-derived CCL5 inhibited the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF1α) by binding to specific receptors, maintained HIF1α under normoxia, thereby up-regulated the downstream gene zinc finger enhancer-binding protein 1 (ZEB1) and induced epithelial-mesenchymal transition (EMT), ultimately validating its ability to promote lung metastasis of HCC. And this novel mechanism may have association with poor prognosis. Taken together, targeting CAF-derived CCL5 mediated HIF1α/ZEB1 cascade possibly propose a new therapeutic route for HCC.”
I certainly don’t know about the HIF1α/ZEB1 axis, but maybe worth a discussion since there’s not much else to talk about. Certainly the data coming from a mouse study will be preliminary and not move any needles soon. But looks like CCR5 blockade of CAF secreted CCL5 may play a role in angiogenesis and poor poor/better prognosis in Glioblastoma at Albert Einstein's.
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